Our goal is the development of a high-throughput automated sequencing instrument adapted for identification of rarely present mutations and polymorphism in mixed populations of DNA molecules and validation of the instrument using the p53 gene as a model system. Operation of the machine is based on a novel detection technique which offers the ultra-high resolution of mixed fluorescent markers. Main features of the machine: . analysis of mixed DNA samples with 1% resolution; . throughput of 6,000,000 bp/year; . low amount of labeled DNA material; . Easy-to-replace capillary cassette; . adapted to color sequencing with different dye sets; In Phase 1 we shall demonstrate a feasibility of 1% resolution of mixed DNA samples and test this detection system using clinical DNA material. In Phase II we shall develop a pilot prototype of the machine and validate the machines using the p53 gene as a model system. In Phase III we shall organize manufacturing of the 12-capillary cassettes and 12-lane automated sequence for diagnostics of mixed DNA samples. PROPOSED COMMERCIAL APPLICATION: The proposed automated sequencing machine will find applications in clinical diagnostics of genetic disease, primarily cancer. Its unique capability to precisely quantify contaminated DNA samples will ensure a dominant position in an important market segment.